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Highly biased CDR3 usage in restricted sets of beta chain variable regions during viral superantigen 9 response
C Ciurli1, D N Posnett, R P Sékaly
1Laboratoire d'Immunologie, Institut de Recherches Cliniques de Montréal, Canada.
Abstract:
Superantigens encoded by the mouse mammary tumor virus can stimulate a large proportion of T cells through interaction with germline-encoded regions of the T cell receptor beta chain like the hypervariable region 4 (HV4) loop. However, several lines of evidence suggest that somatically generated determinants in the CDR3 region might influence superantigen responses. We stimulated T cells from donors differing at the BV6S7 allele with vSAG9 to assess the nature and structure of the T cell receptor in amplified T cells and to evaluate the contribution of non-HV4 elements in vSAG recognition. This report demonstrates that vSAG9 stimulation caused the expansion of TCR BV6-expressing T cells, although to varying degrees depending on the BV6 subfamily. The BV6S7 subfamily was preferentially expanded in all donors, but in donors homozygous for the BV6S7*2 allele, a significant number of BV6S5 T cells were amplified and showed a highly biased beta chain junctional region (BJ) and CDR3 usage. As CDR3 regions are involved in major histocompatibility complex (MHC)-peptide interaction, such a selection is highly suggestive of an intimate MHC-TCR interaction and would imply that the topology of the MHC-vSAG-TCR complex is similar to the one occurring during conventional antigen recognition.
Insights
Mouse mammary tumor virus superantigens activate T cells via T cell receptor (TCR) interactions. This study reveals that specific TCR beta chain CDR3 regions, not just HV4 loops, significantly influence superantigen recognition and T cell expansion.
Area of Science:
- Immunology
- Molecular Biology
- Virology
Background:
- Superantigens from mouse mammary tumor virus (MMTV) activate T cells by binding to germline-encoded T cell receptor (TCR) beta chain regions like HV4.
- Evidence suggests that somatically generated determinants in the TCR's CDR3 region may also impact superantigen responses.
Purpose of the Study:
- To investigate the role of non-HV4 elements, specifically CDR3 regions, in vSAG9 recognition.
- To analyze the structure and nature of TCRs in T cells amplified by vSAG9 stimulation.
- To evaluate the contribution of different BV6 subfamilies to vSAG recognition.
Main Methods:
- Stimulation of T cells from donors with varying BV6S7 alleles using vSAG9.
- Assessment of TCR structure and T cell receptor beta chain junctional region (BJ) and CDR3 usage in amplified T cells.
Main Results:
- vSAG9 stimulation led to the expansion of TCR BV6-expressing T cells, with preferential expansion of the BV6S7 subfamily.
- In donors homozygous for the BV6S7*2 allele, BV6S5 T cells were significantly amplified.
- Amplified BV6S5 T cells exhibited biased BJ and CDR3 usage, suggesting a role in MHC-TCR interaction.
Conclusions:
- vSAG9 recognition involves not only germline-encoded TCR regions but also somatically generated CDR3 determinants.
- The observed biased CDR3 usage implies a significant role for MHC-TCR interaction in vSAG recognition, mirroring conventional antigen recognition pathways.